Single photon emission computed tomography, SPECT, allows for the measurement of the 3-D distribution of radioactive tracers in brain. Tracers in use fall into two main classes. In the first class, the tracer is taken up in brain in proportion to blood flow and thus can be utilized as a marker of neural activity. The second class of tracers binds to neurotransmitter receptors in brain such that the activity then reflects the distribution of the related neurochemistry. While previous work with cerebral blood flow agents was largely successful, other more sensitive means now exist for CBF measurements. Therefore, SPECT imaging has become our procedure of choice for in vivo neurochemistry. In clinical populations, we have performed studies with three radioligands. These include the dopamine D2 antagonist IBZM, the dopamine and serotonin transporter antagonist beta-CIT, and the muscarinic antagonist IQNB. We have used these radioligands to examine clinical correlates of neurochemical function in drug-free schizophrenia patients, and to further elucidate the mechanism of action of neuroleptic drugs. We have just completed a placebo controlled study of serotonin transporter availability in normal subjects taking St. John's wort. We are in the process of finishing a study of pre- and post-synaptic dopaminergic markers in controls subjects and schizophrenia patients. In the past, we have studied dopaminergic and serotonergic function in patients with Tourette syndrome and alcohol dependence. In non-human primate studies with these ligands we have tested neurochemical function in models of human neuropsychiatric illness. We have also conducted non-human primate studies to develop new radioligands. These include TISCH, a dopamine D1 receptor antagonist, and DOI, a serotonin 5HT2 agonist.